Improving Prognosis of Progression Risk in Multiple Myeloma Precursors through Single Cell Sequencing-Based Genomic and Immune Microenvironment Profiling
Basic Information
Description
The accurate stratification of multiple myeloma (MM) patients by progression risk, into Monoclonal Gammopathy of Undetermined Significance (MGUS) with lower disease burden of 1% progression to MM and Smoldering Myeloma (SMM) with a 10% risk of advancing to MM, remains an urgent clinical need. Basing this stratification on whole genome sequencing (WGS) combined with single cell RNA sequencing (scRNAseq) has shown promise but faces two limitations: 1) the sensitivity to define intrapatient genomic heterogeneity is limited, therefore variants in the genome that are present only in small subclones, but with the potential to expand and progress to MM, will be missed. 2) scRNAseq captures phenotypic heterogeneity, but fails to discover most key genomic drivers. We will therefore pursue single cell WGS by Direct Library Preparation (DLP) platform(Laks et al. 2019) to define genomic evolution (Aim 1) and a combination of scWGS and scRNAseq to characterize the early interplay between genomic features and the immune system (Aim 2).
